ACCESSION NO: 0201885
SUBFILE: CRIS
PROJ NO: LAB93719
AGENCY: CSREES LA.B
PROJ TYPE: MCINTIRE-STENNIS
PROJ STATUS: NEW
START: 01 JAN 2005
TERM: 31 DEC 2009
FY: 2005
INVESTIGATOR: Liu, Z.
PERFORMING INSTITUTION:
RENEWABLE NATURAL RESOURCES
LOUISIANA STATE UNIVERSITY
BATON ROUGE, LOUISIANA 70893
FRACTIONATION OF BIOACTIVE BOTANICAL INGREDIENTS UNDER THE DIRECTION OF BIOACTIVITY ASSAYS
NON-TECHNICAL SUMMARY: The current healthcare and agrochemical products are far from efficacious at safe doses. This project focuses on finding effective ingredients from those generally regarded as safe food and plant sources.
OBJECTIVES: The goal of this project is to create new agrochemical and pharmaceutical products from plant based natural chemicals. Native plants and exotic medicinal plants that have been used or indicated to possess promising bioactivities will be prepared, tested, and developed. At the completion of this project, ten bioactive medicinal plants are expected to be ready to enter human clinical studies or field trials.
APPROACH: To achieve the goal the following approaches will be taken in sequence. First, we will identify native or exotic plants based on knowledge of empirical or folklore use for maximum chance of finding hits. We will then prepare plant extracts for biomedical or agrochemical evaluations through collaborations. Such collaborations will direct the isolation processes of the bioactive ingredients and result in the elucidation of the bioactive ingredients. When this is successful, we will proceed to develop standardization protocols for bioactivity-specific plant extracts for application studies. At this stage, we will simultaneously perform cultivation studies for these potential plants for agrochemical or pharmaceutical applications.
PROGRESS: 2005/01 TO 2005/12
Modern laboratory studies have confirmed the benefits and possible modes of action of botanical extracts for human healthcare, but turning them into practical treatments faces two major obstacles, both typical in the use of botanical extracts for healthcare and therapeutics. First, the botanical extracts are not standardized with reference to the active ingredients. Manufacturing without knowledge of what is responsible in the apparent active botanical extracts risks the loss of the key ingredients in the process and results in inconsistent clinical effects. Second, underdosing may have been a major problem in observing clinical effects of many promising botanical extracts observed in laboratory studies. In 2005, the following were accomplished. (1) Scientists from LSU campuses collaborated to fractionate and isolate antiangiogenic agents from several botanical extracts. One of the angiogenic inhibition applications is to suppress the growth of tumors, which require the formation of new blood vessels to supply the needed nutrients and oxygen. My lab applied column chromatography techniques in the isolation, and labs at the Health Sciences Center in New Orleans and Pennington Biomedical Research Center provided assay support to direct the isolation process. (2) My lab developed a standardized protocol for black raspberry extract using an active chemical marker, and manufactured back raspberry extract with this protocol. This standardized berry extract was preliminarily tested at the LSU Health Sciences Center in a tumor-bearing rat model (human pancreatic carcinoma) and was found to inhibit tumor growth and provide a 30% longer lifespan during the 28 day study. (3) A Chinese blackberry leaf tea extract was standardized and manufactured in my lab, and the standardized leaf extract was tested for safety in a pilot human trial by Dr. Eugene Woltering at the LSU Health Sciences Center. Twelve subjects were enrolled in the study based on an approved Institutional Review Board protocol. After almost 6 months of ingesting the leaf extract at a dose of 12 capsules per day, none complained of side effects to their doctors, indicative of good safety. (4) My lab developed a 'Super Noni' technology, by which the noni fruit's antiangiogenic ingredients were concentrated 100 fold. This 'Super Noni' extract was manufactured and tested in a rodent model for absorption and safety. 'Super Noni' fruit extract was safe and had satisfactory absorption properties through oral routes. (5) I collected and extracted eight Louisiana native salt marsh plants. Extracts from these plants were tested against five fungal species in cell cultures at two USDA research laboratories (Dr. David Wedge at the Natural Product Utilization Unit at Oxford, MS and Dr. Anthony De Lucca at the Southern Regional Research Center in New Orleans). One of the extracts was found to be fungicidal and round-one fractionation separated the fungicidal activities into concentrated fractions. (6) Fifty plant extracts were prepared in my lab and was sent to Dr. Kenneth Eilertsen of the Pennington Stem Cell Laboratory to test for major anti-cancer activities.
IMPACT: 2005/01 TO 2005/12
Overcoming the quality control and underdosing issues of botanical extracts is likely to result in successful clinical results. The 'Super Noni' technology, for example, is currently being considered for technology transfer. If finalized, this technology will enter the product development pipeline by the company. Successful launch of this product will not only create business opportunities but also help millions of cancer survivors who need better tools to manage cancer.
PUBLICATIONS: 2005/01 TO 2005/12
1. Qiong WU, Da-Xu FU, Ai-Jun HOU, Guang-Qing LEI, Zhijun Liu, Jia-Kuan CHEN, and Tong-Shui ZHOU. 2005. Antioxidative Phenols and Phenolic Glycosides from Curculigo orchioides. Chem. Pharm. Bull. 53(8): 1065-1067.
2. Liu, Dong, Zhanguo Gao, Jian Zhang, Jianping Ye, and Zhijun Liu. 2005. Bioassay-guided fractionation of the Rubus suavissimus leaf extracts possessing NF-Kappa-B inhibitory activities and a separable cytotoxicity. Pharmaceutical Biology 43(8): 713-717.
3. Liu, Zhijun, Joshua Schwimer, Dong Liu, Frank L. Greenway, Catherine T. Anthony, and Eugene A. Woltering. 2005. Black Raspberry Extract and Fractions Contain Angiogenesis Inhibitors. Journal of Agriculture and Food Chemistry 53(10):3909-3915.
4. Z Li, Z Liu. 2005. Plant regeneration from leaf petiole in Camptotheca acuminata. In Vitro Cellular and Developmental Biology - Plant 41(3):262-265.
5. Lang, Cynthia, Zhijun Liu, H.Wayne Taylor, and David G. Baker. 2005. Effect of Eucommia ulmoides on Systolic Blood Pressure in the Spontaneous Hypertensive Rat. American Journal of Chinese Medicine 33(2): 215-230.
6. Li, Zhanhai and Zhijun Liu. 2005. Camptothecin production in Camptotheca acuminata hydroponic culture and nitrogen enrichments. Canadian Journal of Plant Science 85: 447-452.
7. Xiaojun Wu, Dong Liu, Zhijun Liu. Establishment of a hairy root culture system for producing anti-hypertensive Eucommia extract. Abstract submitted for the American Society of Pharmacognosy meeting, Corvallis Oregon, July 22-27, 2005.
8. Liu, Dong, Joshua Schwimer, Eugene Woltering, Zhijun Liu. Antiangiogenic effect of curcumin in pure versus in extract forms. Abstract submitted for the American Society of Pharmacognosy meeting, Corvallis Oregon, July 22-27, 2005.
9. Andrew T. Roberts, Mary K. Caruso, Ying Yu, Eugene A. Woltering, Zhijun Liu, Joshua E. Schwimer, Drake E. Bellanger, Thomas S. Guillot, and Frank L. Greenway. VALIDATION OF AN ANGIOGENESIS ASSAY BASED ON HUMAN FAT TISSUE. Abstract at the NAASO's 2005 Annual Scientific Meeting.
10. Liu, Zhijun, Conrad Hornick, and Eugene Woltering. 2005. Noni tree: potential cancer preventative, therapy. Louisiana Agriculture 48 (1): 8-9.
PROJECT CONTACT:
Name: Liu, Z.
Phone: 225-578-4214
Fax: 225-578-4227
Email: zhiliu@lsu.edu